The role of the orbital gyrus in the cortical modulation of hypoxic ventilatory control is being studied, a) by determining single cell evoked potentials in response to carotid body stimulation, b) by determining the effect of discrete cortical lesions on hypoxic ventilatory response in conscious animals, and c) by studying the effect of discrete cortical lesions on the attenuation of hypoxic response which occurs in cats acclimatized to simulated high altitude. A study is also being made of diencephalic mechanisms to respiratory regulation by studying the increase of inspiratory tonus which occurs during acute hypoxic exposure under conditions of altered states in the hypothalamus, as for example, sleep. On the basis of a theoretical model which has been proposed, various hypotheses concerning the different effects of general "arousal", as compared with excitation of inspiratory neurones, will be evaluated. Experimental hyperthermia is also used as an experimental tool in this regard. Finally, metabolic effects in the brain, particularly in regard to K ion and lactic acid, are being studied as determinants of certain respiratory phenomena important in the control of breathing.